Abstract
The efficient and selective C-H silylation of heteroarenes, especially the pharmaceutically relevant electron-deficient heteroarenes, represents a great challenge in organic synthesis. Herein we wish to report a distinctive visible light-promoted photocatalytic C-H silylation approach that enables the direct coupling of trialkylhydrosilanes with both electron-deficient and -rich heteroarenes as well as with cyano-substituted arenes in moderate to high yields and with good regioselectivity. The protocol features operational simplicity, mild reaction conditions, and the use of safe and readily available Na2S2O8, bis(trimethylsilyl) peroxide (BTMSPO) or iPr3SiSH as the radical initiators. Notably, the challenging bulky and inert trialkylhydrosilanes, such as (t-butyldimethyl)silane ( t BuMe2SiH) and (triisopropyl)silane (iPr3SiH), work smoothly with the protocol. Moreover, despite the higher stability of t BuMe2Si silylation products, our studies revealed their great reactivity and versatility in diverse C-Si-based chemical transformations, providing an operationally simple, low-cost, and environmentally benign synthetic technology for molecule construction and elaboration.
Highlights
IntroductionHeteroaryltrialkylsilanes, especially the electron-de cient heteroaryltrialkylsilanes, represent a class of promising therapeutic agents with interesting biological properties (see the representative examples shown in Scheme 1).[1,2,3,4] these organosilicon functionalities serve as versatile heteroaryl handles for complex molecule synthesis owing to their high air and moisture stability, low toxicity, and ease of manipulation.[5,6,7,8,9]
Heteroaryltrialkylsilanes, especially the electron-de cient heteroaryltrialkylsilanes, represent a class of promising therapeutic agents with interesting biological properties.[1,2,3,4] these organosilicon functionalities serve as versatile heteroaryl handles for complex molecule synthesis owing to their high air and moisture stability, low toxicity, and ease of manipulation.[5,6,7,8,9]The direct coupling of readily available and unfunctionalized heteroarenes with simple trialkylhydrosilanes offers a stepefficient and atom-economical synthetic tool to access this class of valuable targets
We wish to report a distinctive visible light-promoted photocatalytic C–H silylation approach that enables the direct coupling of trialkylhydrosilanes with both electron-deficient and -rich heteroarenes as well as with cyano-substituted arenes in moderate to high yields and with good regioselectivity
Summary
Heteroaryltrialkylsilanes, especially the electron-de cient heteroaryltrialkylsilanes, represent a class of promising therapeutic agents with interesting biological properties (see the representative examples shown in Scheme 1).[1,2,3,4] these organosilicon functionalities serve as versatile heteroaryl handles for complex molecule synthesis owing to their high air and moisture stability, low toxicity, and ease of manipulation.[5,6,7,8,9]. The process is performed at high temperature (110 C) using a large excess of DTBP (7.0 equiv.), which causes signi cant safety concerns, as well as the difficulty controlling regioselectivity In this eld, there is an unmet synthetic challenge for the development of a mild and truly efficient approach for the selective C–H silylation of heteroarenes, especially the pharmaceutically relevant electron-de cient heteroarenes. Such a method enabling the incorporation of the challenging bulky trialkylsilyl functionalities into heteroarenes will streamline the synthesis of synthetically and medicinally valuable heteroaryltrialkylsilanes, such as the anticancer drug candidate camptothecin derivative DB-67 (Scheme 1).[4] Towards this end, we wish to report a distinctive visible lightpromoted photocatalytic Minisci-type approach that enables the efficient and selective C–H silylation of both electronde cient and -rich heteroarenes in moderate to high yields and with good regioselectivity by using trialkylhydrosilanes (Scheme 2c).
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